Hyaluronic acid is a non-sulfated glycosaminoglycan formed by a disaccharide straight sequence of 1-3-glucuronic acid bonded to N-acetylglucosamine. Hyaluronic acid is ubiquitous in epithelial and connective tissues, e.g., but not only, in skin and cartilages.
Macrogol is the International Non-proprietary Name (INN) of polyethylene glycol, conventionally abbreviated as PEG or PEO.
Macrogol having high molecular weight, in particular macrogol 3350, is used in therapy as a laxative to treat constipation, in particular chronic constipation and is commercialized for example under the Movicol® trademark. In order to obtain the laxative effect, macrogol is administered in a daily dose of 13.7 g-27.4 g daily (one or two sachets of Movicol® containing 13.7 g of macrogol daily). On the other hand, for the pediatric administration, macrogol is provided in 6.9 g sachets to be administered one or two times a day, depending upon the subject age and weight. Macrogol 4000 is also commercialized with the trademark Isocolan® as 34.8, 17.4 and 8.7 g sachets; the 34.8 g dose is considered suitable for the treatment of chronic constipation in adults, whereas the 17.4 and 8.7 g sachets are suitable for pediatric administration.
All the sachets are administered in admixture with water.
In order to carry out the preoperative bowel preparation or for diagnostic tests (colon cleansing), it is used as macrogol 4000 (Isocolan®) in a dose of about 280 g (8 sachets of 34.8 g), dissolved in abundant water.
Although it is a very effective drug for the treatment of constipation, at the therapeutic doses required in order to obtain the desired therapeutic effect, macrogol causes a hydrosaline imbalance, since it acts as osmotic agent keeping water in the colon; the amount of water and electrolytes embedded by macrogol, which directly depends upon the taken dose, can possibly cause a resulting arrhythmia and a reduced blood volume.
In order to try to overcome side effects, pharmaceutical compositions containing macrogol are added with electrolytes, such as sodium sulfate anhydrous, sodium bicarbonate, sodium chloride, potassium chloride and/or ascorbic acid. However, the possible hydrosaline imbalance caused by the intake of high doses of macrogol results in the fact that it must be used with great care in children, and in debilitated subjects, in elderly people, in kidney patient and heart patients. In addition to a possible hydrosaline imbalance, at the used doses, macrogol can produce abdominal bloating and pain and nausea.
There is therefore the need to optimize the therapeutic use of macrogol, e.g. by reducing doses to be administered while maintaining a valuable effectiveness against constipation.